DESCRIPTION: Structural changes accompany, and are assumed to be important for, certain types of long-term synaptic plasticity. The synapse of the mechanosensory neuron (SN) on the gill motor neuron (L7) in the central nervous system of Aplysia has been one of the most productive preparations for studying long-term synaptic plasticity. Large changes in the number of synaptic varicosities and the size of the axonal arbor accompany both facilitation and inhibition of this synapse. New methodological capabilities allowing high resolution imaging of the cells will be used to examine how structural changes occur at the cellular and molecular levels and how they contribute to the expression of plasticity. Recent data point to the importance for structural change of rapid changes in actin dynamics at presynaptic varicosities. The molecular underpinnings of these changes will be examined. Along with this rapid, local change at the terminal, protein synthesis induced in the cell body of the presynaptic neuron by the plasticizing stimulus is required for the growth of presynaptic varicosities and axonal arbor. Which aspects of this growth depend on this protein synthesis will be assessed. New presynaptic varicosities must persist days or more to contribute to long-term facilitation. Experiments will examine the hypothesis that levels at the new varicosities of the adhesion molecule apCAM are involved in maintaining the varicosities. Lastly, the contribution of structural changes to the maintained expression of long-term facilitation will be assessed by blocking those changes. Synaptic plasticity is likely a cellular mechanism for learning, with long-term plasticity underlying memory. By contributing to a cellular and molecular understanding of learning and memory, findings from this project might contribute to the design of therapeutic approaches for disorders of cognitive function, like Alzheimer's disease.